Recovery of nicotinic acid by solvent extraction



Patented Dec. 16, 1952 RECOVERY OF NICOTINIC ACID BY SOLVENT EXTRACTIONMillard S. Larrison, Whippany, N. J assignor to Allied Chemical & DyeCorporation, New York, N. Y., a corporation of New York Application July21, 1949, Serial No. 106,010

13 Claims.

This invention relates to the recovery of nicotinic acid from aqueoussolutions thereof containing inorganic impurities.

It is known to produce pyridine carb-oxylic acids b the oxidation ofN-heteroaryl compounds having an oxidizable organic grouping attached tothe nitrogen-containing aromatic nucleus by at least onecarbon-to-carbon linkage. Of these pyridine carboxylic acids, nicotinicacid is probably the best known at the present time, being a member ofthe vitamin B complex. Nicotinic acid is generally produced by theoxidation of quinoline or a beta alkyl pyridine, such as beta picoline,with an inorganic oxidizing agent such as potassium permanganate, nitricacid or sulfuric acid.

The reaction products obtained in such processes contain, in addition tothe desired nicotinic acid, considerable amounts of water-solubleinorganic impurities, in the form of salts, for example, sodium orammonium sulfate, etc., which are formed upon partially neutralizing theoxidation mass preliminary to recovery of the nicotinic acid therefrom.Such inorganic impurities must be removed to obtain a U. S. P. grade ofnicotinic acid.

Heretofore, removal of such impurities has been accomplished byprecipitating the nicotinic acid as copper nicotinate, separating thecopper nicotinate from the aqueous solution containing the inorganicimpurities and then recovering nicotinic acid from the copper nicotinateby treatment of the copper salt with hydrogen sulfide or by reactionthereof with sodium hydroxide followed by acidification. This recoverymethod, however, is somewhat cumbersome, since it involves recovery ofthe precipitated copper nicotinate and subsequent conversion thereofback to nicotinic acid.

It is an object of this invention to provide a simple and effectivemethod for recovering nicotinic acid from aqueous solutions thereofcontaining water-soluble inorganic impurities.

It is a further object of my invention to provide a method forrecovering nicotinic acid from solutions thereof containing sodium orammonium sulfate.

In accordance with my invention, nicotinic acid is recovered from anaqueous solution thereof containing water-soluble inorganic impuritiessuch as inorganic salts of mineral acids, particularly alkali metal orammonium sulfates and the like, by extracting the nicotinic acid fromthe solution with a normally liquid saturated aliphatic alcoholcontaining from four to six carbon atoms, inclusive, and having at leasta slight solubility in water at 20 C., but not more than about grams perliter of water. Although, in general, nicotinic acid is less soluble insuch alcohols than in water, I have found that when such alcohols arecontacted with an aqueous pyridine carboxylic acid solution containinginorganic impurities, particularly those of the character of sodiumsulfate or the like, the water which dissolves in the alcohol produces amixed alcohol water phase in which the nicotinic acid is surprisinglysoluble; more so than in the water solution containing the impurities asdescribed, and so much so, particularly at elevated temperatures, thatsubstantially quantitative extraction of the nicotinic acid, free ofinorganic impurities, from the aqueous solution may be accomplished withuse of moderate amounts of the alcohol solvent. The nicotinic acid maythen be recovered from the alcoholic solution either by evaporating thesolvent in any suitable manner or by re-extracting the acid from thealcoholic solution with water.

Since it has been found that production of nicetinic acid by oxidationof N-heteroaryl substances such as beta picoline or quinoline withsulfuric acid in the presence of a catalyst is an extremely effectivemanner of producing this acid, a preferred embodiment of my inventioninvolves recovery of nicotinic acid from the oxidation mass produced inthis manner by adjusting the pH value of the oxidation mass to a pointnear the isoelectric point of the nicotinic acid, namely, between about3.0 and about 4.0 and then extracting the mass with an alcohol of thetype above described.

The nicotinic acid solution treated in accordance with this inventionmay be any aqueous solution of nicotinic acid containing water-solubleinorganic impurities of the character described, from which it isdesired to recover the acid. The solution treated should containsubstantially all the nicotinic acid in the form of the freeacid and, inaddition, should be prac-. tically free of unneutralized inorganic acidssuch as sulfuric or nitric acid. Accordingly, the pH value of thesolution treated should be at approximately the isoelectric point asbrought out above, i. e., between about 3.0 and about 4.0, preferablyabout 3.5, and, if necessary, alkali or acid should be added to theaqueous solution in order to bring the pH value to within this rangebefore contact with the aliphatic alcohol. If desired, the nicotinicacid solution may be subjected to preliminary purification treatments,for

example, a decolorization treatment with active carbon, prior totreatment of the solution with aliphatic alcohol,

As above noted, the aliphatic alcohol employed in accordance with myinvention may be any normally liquid saturated aliphatic alcoholcontaining from four tosix carbon atoms, inclusive, and having at leasta slight solubility in water at 20 C. but not more than about 125 gramsper liter, or mixtures of such alcohols. Thus 1 or 2 butanol, iso-butylalcohol, the pentanols' and the hexanols, including cyclohexanol, maybe.employed in accordance with this invention. Tertiary butyl alcohol isnot suit-able for use inaccordance with this invention because of itshigh solubility inwater, this being greater than the limitationmentioned above. n-Butanolis-preferably employed in the practice of myinvention. Another preferred solvent which may advantageously be used,is the mixture of pentanols sold under the trade name Pentasol, the approximate analysis of which is as follows: 1- pentanol, 26%; Z-pentanol,8%; 3-pentanol, 18%; ii-methyll-butanol, 1.6%; and. Z-methyll-butanol,32%.

Extraction of" the aqueous nicotinicacid solutionwith the saturated"aliphatic alcohol inaccordancewith the invention ispreferably effectedby passing the nicotinic acid-containing solution and alcohol solventcountercurrently through a suitable vessel to eifectclose liquid-liquidcontact. In this extraction I prefer to use an excess of alcohol-solventover the nicotinicacid-containing solution,.preferably in. the ratioofsbetween somewhat above 1: volume of. alcohol to 1. volume ofnicotinic acid-containing solution and-about 1.5 volumes of alcoholto 1. of nicotinicacid-containing. solution. Larger excesses of alcoholmay be used if desired but this. practice presents. the disadvantage ofrequiring th handling of larger volumes of. solvent, and of recoveringlarger. quantities of. alcohol for reuse. The temperature at whichextraction is. carried out. may. vary between about 40? and. aboutlOO?C. depending, inter. alia,, on. the, alcohol used, and I. have foundthatthe useofelevated temperatures of the. order offia" to 95? C.improves the sclubilityofnicotinic acid in the alcoholsolvent and.minimizes any tendency for inorganic impuritie such-as. sodium sulfate.to. precipitate. The aqueous raifinate stripped of itsnicotinic. acid.content. is removed from the extraction. vessel andmay be..discarde.d;although it is usuallydesirable to. treat. this raffinate,.for. example,by steam distillation,.to..recover a y ofthe alcohol solvent dissolvedtherein.

The alcoholic solution of nico-tinic acidthus obtained may be treated inany suitable. manner to recover the nico-tinic acidand thealcoholsolvent. Thus the alcohol-may be evaporated-from the nicotinic.acid to. produce a substantially dry residue containing. a small amountof alcohol therein; the, dried acid. may then be either taken up in.water. and recovered by crystallization or agitated with water to form aslurry, which is then centrifuged, the residual alcohol beingseparatedfromithe.acidin the aqueousphase; or. the alcohol solution maybe partially evaporatedrto aslurry. and acrude,dry.-nicotinic-acid.thenpro duced by drum. drying the.- slurry.Inboththe above. instances, it is desirable that, the alcohol evaporatedbe. Condensed for re-use in order to improve the economics of theprocess... The ,alcoholsolutionmay, if desired, be partially evaporateduntil the rate ofeva oration slows down appreciably; and the residuethen steam distilled ous layer, containin a small amount ofalcoholdissolved therein,v used in subsequent steam distillation.

My preferred procedure, however, for recoveringv the nicotinic acid fromthe alcoholic solution is to. extract such solution with water,preferably at temperatures which result in effective transfer ofnicotinic acid from the alcohol to the water solution. While suchtransfer may satisfactorily be effected at temperatures from about 55 C.up to about the boiling point of the alcohol used, I prefer to carry outthe extraction at temperatures between about 65 C. and C. At weightratios of water to alcohol solution above about 1 to-l a highdegree'oftransfer of nicotinic acid to the water phase, may be achieved. I preferto use countercurrent extraction with an excess of water over alcoholsolution, preferablya-ratio of about 1.5 of water to 1- of alcohol, atwhich ratio substantially complete transfer is obtained. Larger excessesof water may be used if desired and improve theefiiciency of transfersomewhat, but this practice also presents the'difliculty-of recoveringthe acid from more dilute. solutions. The aqueous solution. of nicotinicacid thus formed may then be concentrated, cooled and subjectedtocrystallization or other treatment to recover the acid.

The accompanying drawing illustrates diagrammatically a flow sheet ofthe preferredembodiment of this invention. As shown in the drawing,crude oxidation mass resulting, for ex ample, from catalytic sulfuricacid oxidationof beta picoline or quinoline andcontainingnicotinic acid,sulfuric acid, etc, is introduced into drowning tank I, containing anexcess of-water, for example, between about'5 and about 10 timesthevolumeof nicotinic acid solution, along, with sodium hydroxide inamounts-sufficient to forma solution having a pH value 'of about 3.5,there by neutralizing the bulk of .the unreacted sulfuric acid, formingsodium sulfate, but. leaving substantially'all of the nicotinic acid'inunneutralized form. Active carbon 'andlmother liquor, r'ecovered fromsubsequent steps in the operation, are then introduced into drowningtank I and the mass thoroughly agitated. From drowning tank I the slurrypasses to filter 2, in. which the active carbon is removed anddiscarded. The aqueous solution of nicotinic acid and sodium sulfate isthen heated to a temperature between 95 C. and C. and introduced intothe top of column 3; n-butanol, heated to a temperature of about 45 C.,is introduced at the bottom of the column, the butanol and aqueoussolution thereby passing countercurrently through column 3'; thetemperature of the column varies from 80 to 100 C. at'the top to about45 C. at the bottom.

The. aqueous solution, stripped of its nicotinic acid, may be discardedor it may be treatedto recover the dissolved butanol in which case-it ispassed from column 3 to still 4, wherein it is steam distilled to removethe butanol. The stripped aqueous sodium sulfate solution is then eitherdiscarded or the sodium sulfate contained therein. recovered. The waterdistillate containing traces of butanol is condensed in condenser 5' andpassed to the top. of. column 6, where it isadmixed with additionalwater andthe mixture tions thereof in butanol.

' heated to about 75 C. The mixture, consisting primarily of water, isthen introduced into the top of column 6. The solution of nicotinic acidin butanol, withdrawn from column 3 is introduced at a temperature ofabout 75 G. into the bottom of column 6, and passes upwardlytherethrough countercurrent to the descending stream of water, giving upits nicotinic acid to the water phase. The solution of nicotinic acid inwater, free of inorganic impurities, is withdrawn from the bottom ofcolumn 6 and is passed to concentrator I for treatment described below.n-Butanol, stripped of its nicotinic acid content, is

" withdrawn from the top of column 6 and returned to column 3 for re-usetherein.

In concentrator 1 the aqueous nicotinic acid solution is evaporated to aconcentration of between about and about nicotinic acid.

The distillate passing from this concentrator,

consisting of butanol and water, is condensed in condenser 8 and passedto separator 9, wherein the condensate is permitted to settle, anaqueous layer and a butanol layer being formed; the aqueous layer iswithdrawn from separator 9 and 'returned to column 6, as shown, whereinit is used for extracting nicotinic acid from solu The butanol layerfrom separator 9 is returned to column 3 for re-use.

The concentrated aqueous nicotinic acid solution from concentrator l ispassed to treater In, in which it is agitated with activated carbon. Theslurry is then passed to filter ll, wherein the carbon is removed byfiltration, the carbon filter cake being used in drowning tank I todecolorize the crude oxidation mass. 'The aqueous nicotinic acidsolution is passed from filter l l to crystallizer I2, wherein it iscooled to crystallize the acid; pure nicotinic acid is recovered fromthe cooled slurry in filter 13, the mother liquor being returned todrowning tank I.

The following example is illustrative of my invention:

- EXAMPLE A reaction mass containing nicotinic acid and free sulfuricacid, resulting from oxidation of quinoline with sulfuric acid in thepresence of a selenium catalyst, was drowned in about 8 volumes of waterand caustic soda was added thereto to produce a solution having a pHvalue of 3.5;

the bottom of the tower was also commenced, the

' butanol being fed to the column at a temperature of C. and at a rateof 10 gallons per hour. The aqueous solution and n-butanol passedthrough the column countercurrently, a butanol extract containing thenicotinic acid dissolved therein being withdrawn from the top of thecolumn, and an aqueous raifinate being removed from the bottom of thecolumn and discarded.

The butanol extract withdrawn from the top of the column was passed tothe bottom of a second column 12 it. high and packed with .10 ft. ofBerl porcelain saddles, the extract being introduced at a temperature of75 C. and at a rate of 10 gallons per hour; water, also preheated to atemperature of 75 (3., was pumped into the top of the column at a rateof 15 gallons per hour, the water and butanol extract thus passingcountercurrently through the column. The butanol rafflnate withdrawnfrom the top of this column was recovered for reuse in extractingadditional quantities of crude aqueous nicotinic acid solution. Theaqueous extract withdrawn from the bottom of the column was concentratedby evaporation to produce a liquor containing 0.5 pound of nicotinicacid per gallon; the concentrated solution was then decolorized withactivated carbon and filtered. The filtrate was cooled to 5 C. and thenicotinic acid which crystallized was recovered in a centrifuge, themother liquor being recovered for use in drowning subsequent crudeoxidation products. The nicotinic acid thus obtained had a melting pointof 236.5 C. and analyzed substantially 100% nicotinic acid; it containedvirtually no sodium sulfate, chlorides or heavy metals.

As brought out above, it is indeed surprising that nicotinic acid can beextracted efficiently substantially quantitatively since solubility ofnicotinic acid in these alcohols is less than its solubility in water.The efi'iciency obtained by such extraction is made possible by thesurprising discovery that the solubility of nicotinic acid in thealcohols saturated with water, is greater than that in the anhydrousalcohols, especially at elevated temperatures as indicated in Table Ibelow:

Table I [Approximate Solubilities of Nicotinie Acid in (a) water, and(b) ali hatic a] h l water free, and (c) aliphatic alcohols saturatedwith water, at nom nal and st elei a t c e t i ngz r ax tures,respectively] Solvent Medium Solubility, grams Nicotinic Acid per 100grams Solvent N-Hexanol 2-M ethyliso-butylcarbinol- 2-E thyl-l-butanolMixed Pentauols (Pentasol) i this solution was then agitated withactivated carbon and filtered. The filtrate, containing 0.325 pounds ofnicotinic acid per gallon, was preheated to a temperature of 95 C. andthen pumped into the top of an 11 ft. column packed with 9.65 ft. of /g"Berl porcelain saddles and filled with n-butanol at a temperature of C.,

the filtrate being introduced at a rate of 7.5 gal- The term normallyliquid aliphatic alcohol is used throughout the specification and claimsto denote an aliphatic alcohol which is liquid at a temperature of 20 C.

Since certain changes may be made in carrying out the above processwithout departing from the scope of the invention, it is intended that.lons per hour. Introduction of n-butanol into all matter contained inthe above description .shall Joe interpreted .as illustrative and not.in

.a limiting sense.

'I-claim:

:1. In a process for recovering nicotinic acid "from an aqueous solutionthereof containing water-soluble inorganic impurities, the steps whichcomprise-extractin atan initial pH valve between about 3.0 and about 4.0the aqueous solution with a water-wet normally liquid saturatedaliphatic alcohol containing from four to -six:ca-rbonatomsinclu-sive,-a-nd having a solubility inwater :at C. of not more thanabout 1125 .grams per liter, whereby a solution of nicotinic acid :inthe alcohol substantially free of inorganic impurities is obtained.

,2. in :aprocess for recovering nicotinic acid from an aqueous solutionthereof containing water-soluble inorganic :impurities and having a pHvalue between about 3.0 and about 4.0, the steps which compriseextracting the aqueous solution with a water-wet-normally liquidsaturated aliphatic alcohol containing from four to sixzcarbonatoms-inclusive, and having a solubility in-water at 20 C. of not morethan about grains per liter, whereby a solution of .nicotinic acid inthe alcohol substantially free 'ofinorganic impurities-is obtained, andrecovering nicotinic acid from the alcohol solution thereof.

3. In a process for recoverin nicotinic acid from an aqueous solutionthereof containing sodium-sulfate "and having a pH value between about3.0 and about 4.0 the steps which com- .prise countercurrentlyextracting the aqueous solution with a'water-wet normally liquidsaturated aliphatic alcohol containing from four to six carbon atomsinclusive, and having a sol- .ubility in water at 20 C. of not more thanabout 125 grams per liter, at temperatures between .about.40.C. andabout 100 C., whereby a solution of nicotinic acid in the alcoholsubstantially free of inorganic impurities is obtained, and thenextracting said solution with water at temperatures between about 575 C.and about 95 C., so as to produce an aqueous solution of nicotinic acidsubstantially free of inorganic impurities.

4. In a process for recovering nicotinic acid from an aqueous solutionthereof containing water-soluble inorganic impurities, the steps whichcomprise adjusting the pH yalue to between about S.0 and about 4.0,extracting the aqueous solution with water-wet n-butanol, whereby asolution of nicotinic acid in the butanol substantially free ofinorganic impurities is obtained, and recovering nicotinic acid from thebutanol solution thereof.

,5. In a process for recovering nicotinic acid from an aqueous solutionthereof containing sodium sulfate and having a pH value between about3.0 and about 4.0, thesteps which comprise extracting the aqueoussolution with water- 'wet n-butanol .at a temperature between about 40C. and about 100 0., whereby a solution of nicotinic acid in the butanolsubstantially free of inorganic impurities is obtained, and thenextracting said solution with water at a temperature between about 55 C.and about 95 C., so as to produce .an aqueous solution of nicotinic acidsubstantially free of inorganic impurities.

6.121 a process for recovering nicotinic acid from an aqueous solutionthereof containing water-soluble inorganic impurities, the steps whichcomprise adjusting the pH value to between about 3.0 and about 4.0,extracting the aqueous solution With-a water-wet pentanol, whereby,asolu- -.tion of nicotinicacid tially free of inorganic impuritiesiscobtained,

in the -pen-tanol substanand recovering nicotinic .acid from the-pentanol solution thereof.

'7. In a processfor.recovering nicotinicacid from an aqueous solutionthereof containing sodium sulfate and having a pH value -:between about3.0 and about 4.0, the steps whichcomprise extracting the aqueoussolutionwitharwater-wet pentanol at a temperature between about-.40 C.and about C., whereby'asolution of nicotinic vacid inthepentanolsubstantially free" of inorthe pH value of the solution tobetween-.about.3.0

and about 4.0'by the'addition .of an alkali, and extracting'saidsolution Witha water-Wet normally liquid saturatedaliphaticalcoholzcontaining from four to six carbonatoms'inclusivegandhaving a solubility inwaterat 20- Cpofnotmore than about grams perliter, whereby: a'solution of nicotinic acid in the alcoholandsubstantially free of-inorganic impurities'istobtained.

9. In a process for'the recovery "of :nicotinic acid from an aqueoussolution'thereof containing free sulfuric acid, the steps which compriseadjusting'the pH value 'of thesolution'to between about 3.0 and about4.0 by the addition of an alkali, countercurrently extracting said:solution with water-wet n-butanol at a temperatureof between about 40C. -:.and about 100 C., withdrawing the butanol extract containing thenicotinic acid but substantiallyno .alkali metal sulfate,countercurrently contacting said butanol extract with Water atatemperaturebetween-about 55 C. and about 95 C. so as to stripthebutanol extract of its nicotinic acid content, recovering thestripped butanol-and recycling it for contact with further quantities-ofthe aqueouscrude nicotinic acid solution, and recoveringpure-nicotinicacid from the aqueous extract thusformed.

10. In a process for therecoveryof nicotinic acid from an aqueoussolution thereof containing free sulfuric acid, the steps which compriseadjusting the pH value of the solution to between about 3.0 and about4.0 by the addition of sodium hydroxide, countercurrently contacting theresulting solution with water-wet n-butanol at a temperature betweenabout 65 C. and about 95 C., using a butanol: water ratio greater than1:1, withdrawing the butanol extract containing the nicotinic acidsubstantially free from sodium sulfate, thereafter countercurrentlycontacting said butanol extract with water at a temperature betweenabout '55 C. and about 95 C. using a waterzbutanol ratio greater than1:1, whereby the nicotinic acid is transferred substantiallycompletelyto the water phase, and recovering the nicotinic acid from theaqueous solution.

11. In a process for recovering nicotinic acid from an aqueous solutionthereof containing at least one of an ,alkali metal sulfate .andammoniumsulfate .and having-a pH valuebetween about 3.0 and about 4.0, the stepswhich comprise countercurrently extracting the aqueous solution with awater-wet normally 'liquid saturated aliphatic alcohol containing fromfour to six carbon atoms inclusive, :andrhaving saxsolubilityrinwater-.at-ZO -C. of not morethan about 125 :grams per liter, attemperatures between about 40 C. and about 100 0., whereby a solution ofnicotinic acid in the alcohol substantially free of inorganic impuritiesis obtained, and then extracting said solution with water attemperatures between about 55 C. and about 95 C. so as to produce anaqueous solution of nicotinic acid substantially free of inorganicimpurities.

12. In a process for recovering nicotinic acid from an aqueous solutionthereof containing ammonium sulfate and having a pH value between about3.0 and about 4.0, the steps which comprise countercurrently extractingthe aqueous solution with a water-wet normally liquid saturatedaliphatic alcohol containing from four to six carbon atoms inclusive,and having a solubility in water at C. of not more than about 125 gramsper liter, at temperatures between about C. and about 100 C., whereby asolution of nicotinic acid in the alcohol substantially free ofinorganic impurities is obtained, and then extracting said solution withwater at temperatures between about C. and about C., so as to produce anaqueous solution of nicotinic acid substantially free of inorganicimpurities.

13. In a process for recovering nicotinic acid from an aqueous solutionthereof containing wator-soluble inorganic impurities, the steps whichcomprise extracting at an initial pH value between about 3.0 and about4.0 the aqueous solu- 10 tion at temperatures between about 40 C. andabout C. with a water-wet normally liquid saturated aliphatic alcoholcontaining from four to six carbon atoms inclusive, and having asolubility in water at 20 C. of not more than about grams per literusing an alcohol: aqueous solution ratio between about 1:1 and about1.5:1, whereby a solution of nicotinic acid in the alcohol substantiallyfree of inorganic impurities is obtained.

MILLARD S. LARRISON.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS 1937, McGraw-Hill.

Perry: Chemical Engineering Handbook, 2nd. edition, 1941, pgs. 1214 and1215.

Chemical Engineering Handbook 3rd. edition 1950, Pp. 714, 715.

1. IN A PROCESS FOR RECOVERING NICOTINIC ACID FROM AN AQUEOUS SOLUTIONTHEREOF CONTAINING WATER-SOLUBLE INORGANIC IMPURITIES, THE STEPS WHICHCOMPRISES EXTRACTING AT AN INITIAL PH VALVE BETWEEN ABOUT 3.0 AND ABOUT4.0 THE AQUEOUS SOLUTION WITH A WATER-WET NORMALLY LIQUID SATURATEDALIPHATIC ALCOHOL CONTAINING FROM FOUR TO SIX CARBON ATOMS INCLUSIVE,AND HAVING A SOLUBILITY IN WATER AT 20* C. OF NOT MORE THAN ABOUT 125GRAMS PER LITER, WHEREBY A SOLUTION OF NIC-